Suzuki-Miyaura cross-coupling reactions of potassium vinyltrifluoroborate with aryl and heteroaryl electrophiles

We have previously reported that the palladium-catalyzed cross-coupling reaction of potassium vinyltrifluoroborate with aryl electrophiles proceeds with good yields. Herein, we describe recent progress in optimizing the reaction, as well as outlining the scope and limitations of the reaction. The cross-coupling reaction can generally be effected using 2 mol % of PdCl2 and 6 mol % of PPh3 as a catalyst system in THF/H2O with Cs2CO3 as a base. Moderate to good yields are obtained in the presence of a variety of functional groups.     

Direct guanidinylation of aryl and heteroaryl halides via copper-catalyzed cross-coupling reaction

A modified Ullmann reaction using p-methoxybenzyl (PMB) guanidine as guanidinylation agent yielded various aryl and heteroaryl guanidines in good yields.     

Synthesis of biphenylamines via Suzuki-Miyaura cross-coupling reactions

A small library of meta- and para-biphenylamines substituted by various alkyl, alkoxy, phenoxy, or halogeno groups on their aromatic rings was synthesized via Suzuki-Miyaura cross-coupling between bromoanilines and arylboronic acids using palladium catalysts. The experimental conditions were carefully adjusted to accommodate a wide range of substituents, in terms of electron-withdrawing or -donating ability and steric bulk. In some cases, protection and deprotection of the amine function via its trifluoroacetamide were added to the reaction sequence in order to facilitate the cross-coupling step.     

Synthesis of S-acetyl oligoarylenedithiols via Suzuki-Miyaura cross-coupling

Oligoarylenes with three or four aromatic rings, bearing two S-acetylated mercaptomethyl groups in 1,3 position on one end of the polyaromatic system and presenting various functionalities on the other terminal ring, have been synthesized by the Suzuki-Miyaura cross-coupling reaction. The use of palladium complexes with a Buchwald's phosphine as ligand allowed us to perform this coupling reaction also in the presence of benzylic S-acetyl-protected functionalities on the aromatic halide. The obtained oligoarylenes are potential novel candidates for the generation of self-assembling monolayers on metal substrates.     

One-pot reductive amination and Suzuki-Miyaura cross-coupling of formyl aryl and heteroaryl MIDA boronates in array format

Formyl-substituted aryl and heteroaryl MIDA boronates were prepared by a DMSO-free method and used in the first reported one-pot reductive amination-Suzuki-Miyaura cross-coupling sequence. This sequence was then carried out in parallel array format, using microwave-assisted in situ release cross-coupling of MIDA boronates to generate a library with diversity along two axes, affording rapid and convenient access to an array of druglike molecules.     

Synthesis of 5-arylhistidines via a Suzuki-Miyaura cross-coupling

Microwave irradiation efficiently promoted the Suzuki-Miyaura reaction of a 5-bromohistidine with various arylboronic acids in the presence of a palladium catalyst. This methodology allowed the synthesis of histidines substituted at position 5 of the imidazole ring with a phenyl, a substituted phenyl, a pyridyl or a thienyl ring. The corresponding 5-arylhistidines were obtained in moderate to good yields.     

Suzuki-Miyaura cross-coupling of heteroaryl halides and arylboronic acids in continuous flow

General continuous-flow conditions for the Suzuki-Miyaura cross-coupling of heteroaryl halides and (hetero)arylboronic acids have been developed. A wide range of heterobiaryl products is obtained in excellent yields (20 examples) employing low catalyst loadings (0.05-1.5 mol % Pd).     

Convenient synthesis of photochromic symmetrical or unsymmetrical bis(heteroaryl)maleimides via the Suzuki-Miyaura cross-coupling reaction

A general method for the synthesis of symmetrical or unsymmetrical bis(heteroaryl)maleimides by a one-pot procedure involving Suzuki-Miyaura cross-coupling sequence was developed on the basis of the reaction of 3,4-diiodo-1-benzyl-1H-pyrrole-2,5-dione with cyclic boronate esters using PdCl₂(dppf) as the catalyst. Photochromic properties of the products were examined.     

Palladium-catalyzed Hiyama cross-coupling of aryltrifluorosilanes with aryl and heteroaryl chlorides

An efficient, palladium-catalyzed Hiyama cross-coupling reaction of aryltrifluorosilanes with aryl chlorides has been developed. A wide variety of functionalized biaryl derivatives were isolated in good to excellent yields. The scope of this reaction has also been extended to heteroaryl chlorides, affording the corresponding heterobiaryl compounds in high yields.     

Synthesis and Suzuki-Miyaura cross-coupling reactions of potassium Boc-protected aminomethyltrifluoroborate with aryl and hetaryl halides

Potassium Boc-protected aminomethyltrifluoroborate, a primary aminomethyl equivalent, was synthesized successfully through a "one-pot" process. With this trifluoroborate, Suzuki-Miyaura cross-coupling reactions were investigated with a variety of both aryl and hetaryl chlorides in good to excellent yields.     

An active ferrocenyl triarylphosphine for palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl halides

Pd-catalyzed Suzuki-Miyaura reaction of aryl chlorides was accomplished through the use of an active ferrocene-based triarylphosphine ligand. This air- and moisture-stable ligand was found to be effective for the cross-coupling of aryl halides at room temperature to 115 degrees C.     

Revisiting the Hirao cross-coupling: improved synthesis of aryl and heteroaryl phosphonates

The palladium-catalyzed cross-coupling of dialkylphosphite with aromatic electrophiles (Hirao coupling) was re-investigated. Some limitations in terms of palladium loadings and substrate reactivity are alleviated with the use of Pd(OAc)₂ complexed to 1,1′-bis(diphenylphosphino)ferrocene (dppf) as a ligand. Various aryl and heteroaryl halides are employed to deliver both known and novel substituted phosphonates. The first examples of aryl chloride couplings are also reported.     

A new catalytic cross-coupling approach for the synthesis of protected aryl and heteroaryl amidines

[reaction: see text] A new method for the synthesis of protected benzamidines is described. The commercially available 1,3-bis(tert-butoxycarbonyl)-2-methyl-2-thiopseudourea guanidylation reagent, after SEM-protection, functions as an amidine-forming cross-coupling partner under Liebeskind-Srogl conditions. In the presence of copper(I) thiophenecarboxylate (CuTC), the palladium-catalyzed cross-coupling of the SEM-protected thiopseudourea reagent with boronic acids affords fully protected benzamidines in good to excellent yield (40-91%).     

Suzuki-Miyaura cross-coupling reactions of aryl tellurides with potassium aryltrifluoroborate salts

[reaction: see text] Palladium(0)-catalyzed cross-coupling between potassium aryltrifluoroborate salts and aryl tellurides proceeds readily to afford the desired biaryls in good to excellent yield. The reaction seems to be unaffected by the presence of electron-withdrawing or electron-donating substituents in both the potassium aryltrifluoroborate salts and aryl tellurides partners. Biaryls containing a variety of functional groups can be prepared. A chemoselectivity study was also carried out using aryl tellurides bearing halogen atoms in the same compound. In addition, this new version of the Suzuki-Miyaura cross-coupling reaction was monitored by electrospray ionization mass spectrometry where some reaction intermediates were detected and analyzed.     

Ferrocence-based phosphine-triazine ligands for highly efficient Suzuki-Miyaura cross-coupling reaction of aryl chlorides

A series of ferrocene-based phosphine-triazine ligands were successfully employed in the Pd-catalyzed Suzuki-Miyaura cross-coupling reaction of aryl chlorides with arylboronic acids, with ligand 1b was demonstrated to be the most effective one. Under optimized reaction conditions, the catalytic system displayed a remarkable tolerance towards electron-donating substituents and electron-withdrawing substituents.     

Synthesis and characterization of aryl thioacetyl styrene monomers: towards a new generation of SERS-active polymers

A new family of thioacetyl styrene derivatives was synthesized in good isolated yields for the preparation of spectroscopically-encoded SERS-active polymers.     

Scope of aminomethylations via Suzuki-Miyaura cross-coupling of organotrifluoroborates

We previously reported the Suzuki-Miyaura reaction of N,N-dialkylaminomethyltrifluoroborates with aryl bromides. Herein, we report a further investigation of the scope and limitations of this palladium-catalyzed aminomethylation reaction. Aryl chlorides, iodides, and triflates coupled in good to excellent yields to give N,N-dialkylbenzylic amines. The aminomethylation of alkenyl bromides was also examined.     

Suzuki-Miyaura cross-coupling of aryl carbamates and sulfamates: experimental and computational studies

The first Suzuki-Miyaura cross-coupling reactions of the synthetically versatile aryl O-carbamate and O-sulfamate groups are described. The transformations utilize the inexpensive, bench-stable catalyst NiCl(2)(PCy(3))(2) to furnish biaryls in good to excellent yields. A broad scope for this methodology has been demonstrated. Substrates with electron-donating and electron-withdrawing groups are tolerated, in addition to those that possess ortho substituents. Furthermore, heteroaryl substrates may be employed as coupling partners. A computational study providing the full catalytic cycles for these cross-coupling reactions is described. The oxidative addition with carbamates or sulfamates occurs via a five-centered transition state, resulting in the exclusive cleavage of the aryl C-O bond. Water is found to stabilize the Ni-carbamate catalyst resting state, which thus provides rationalization of the relative decreased rate of coupling of carbamates. Several synthetic applications are presented to showcase the utility of the methodology in the synthesis of polysubstituted aromatic compounds of natural product and bioactive molecule interest.     

Synthesis of 1,5-disubstituted tetrazoles via Suzuki-Miyaura cross-coupling of 5-chloro-1-phenyltetrazole

Suzuki-Miyaura coupling reactions of 5-chloro-1-phenyl-tetrazole with various functionalized arylboronic acids were investigated. In the presence of catalytic amounts of SPhos/Pd(OAc)₂ or RuPhos/Pd(OAc)₂, the reaction proceeded smoothly to afford 1,5-diaryltetrazoles in good to excellent yields.